Compositions and methods for treating seizure disorders

Abstract

Functional analogs of fenfluramine are provided. The subject fenfluramine functional analogs find use in the treatment of a variety of diseases. For example, methods of treating epilepsy by administering a fenfluramine analog to a subject in need thereof are provided. Also provided are methods of treating a neurodegenerative disease in a subject in need thereof. Pharmaceutical compositions for use in practicing the subject methods are also provided.

Description

FIELD OF THE INVENTION[0001]The present invention relates generally to the therapeutic treatment of patients diagnosed with a seizure disorder. More specifically, the invention relates to therapeutic agents that are functional analogs of the amphetamine drug fenfluramine, and to methods of using those compounds to treat human patients diagnosed with intractable forms of epilepsy.BACKGROUND OF THE INVENTION[0002]Epilepsy is a condition of the brain marked by a susceptibility to recurrent seizures. There are numerous causes of epilepsy including, but not limited to birth trauma, perinatal infection, anoxia, infectious diseases, ingestion of toxins, tumors of the brain, inherited disorders or degenerative disease, head injury or trauma, metabolic disorders, cerebrovascular accident and alcohol withdrawal.[0003]A large number of subtypes of epilepsy have been characterized, each with its own unique clinical symptoms, signs, and phenotype, underlying pathophysiology and distinct response...

AI Technical Summary

Benefits of technology

The therapeutic agents described in this patent are better than other treatments currently available for their effectiveness and safety profile.

Problems solved by technology

That is, while a particular drug can be effective against one form of epilepsy, it can be wholly ineffective against others, or even contra-indicated due to exacerbation of symptoms, such as worsening the frequency and severity of the seizures.

As a result, efficacy of a particular drug with respect to a particular type of epilepsy is wholly unpredictable, and therefore it is an entirely surprising discovery when a particular drug not previously known to be effective for a particular type of epilepsy is found to be effective.

This leads to poor development of language and motor skills.

Children with Dravet Syndrome are likely to experience multiple seizures per day.

Additionally, patients are at risk of numerous associated conditions including orthopedic developmental issues, impaired growth and chronic upper respiratory infections.

The cost of care for Dravet Syndrome patients is also high as the affected children require constant supervision and many require institutionalization as they reach teenage years.

Status Epilepticus can be fatal.

It can also be associated with cerebral hypoxia, possibly leading to damage to brain tissue.

Frequent hospitalizations of children with Dravet Syndrome are clearly distressing, not only to the patient but also to family and care givers.

Although a number of anticonvulsant therapies have been employed to reduce the instance of seizures in patients with Dravet Syndrome, the results obtained with such therapies are typically poor and those therapies only affect partial cessation of seizures at best.

Further, many anticonvulsants such as clobazam and clonazepam have undesirable side effects, which are particularly acute in pediatric patients.

Hence, while fenfluramine is effective as an anti-seizure medication, it also has the potential for causing serious side effects.

Patients who receive fenfluramine must be carefully monitored, which is time-consuming and expensive.

Thus, there is a dire, long felt, but previously unmet need for therapeutic agents effective in treating, preventing or ameliorating the frequent severe seizures suffered by patients with refractory epilepsy syndromes, including but not limited to Dravet syndrome, Lennox-Gastaut syndrome, and Doose syndrome, which are not associated with unwanted side effects.

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